COVID-19 Induces Cytokine Storm and Dysfunctional Hemostasis.

BACKGROUND: Infection with SARS-CoV-2 leads to COVID-19 which can manifest in various ways from asymptomatic or mild disease to acute respiratory distress syndrome. The occurrence of dysregulated inflammatory responses in the form of a cytokine storm has been reported in patients with severe COVID-19. Infection can also lead to dysfunctional hemostasis reflected in elevated circulating D-dimer and fibrin degradation products. Components of hemostasis and the immune system during infection can result in a procoagulation and/or proinflammatory state. The interplay between coagulation and inflammation has been elucidated in a number of diseases. OBJECTIVE: In this article, we discuss the occurrence of cytokine storms and dysfunctional hemostasis induced in COVID-19. METHODS: This review was written using literature from the past two to three years investigating coagulation and inflammation in COVID-19. Additional literature, both clinical and basic research, related to pathogen infection and host responses were also considered in this review. RESULTS/CONCLUSIONS: Infection with SARS-CoV-2 can lead to dysregulated inflammatory responses that may be detrimental to the host. The increased expression of various inflammatory factors can ultimately create an environment that promotes thrombosis.

Spike protein receptor-binding domains from SARS-CoV-2 variants of interest bind human ACE2 more tightly than the prototype spike protein.

Several SARS-CoV-2 variants of interest (VOI) have emerged since this virus was first identified as the etiologic agent responsible for COVID-19. Some of these variants have demonstrated differences in both virulence and transmissibility, as well as in evasion of immune responses in hosts vaccinated against the original strain of SARS-CoV-2. There remains a lack of definitive evidence that identifies the genetic elements that are responsible for the differences in transmissibility among these variants. One factor affecting transmissibility is the initial binding of the surface spike protein (SP) of SARS-CoV-2 to human angiotensin converting enzyme-2 (hACE2), the widely accepted receptor for SP. This step in the viral replication process is mediated by the receptor binding domain (RBD) of SP that is located on the surface of the virus. This current study was conducted with the aim of assessing potential differences in binding affinity between recombinant hACE2 and the RBDs of emergent SARS-CoV-2 WHO VOIs. Mutations that affect the binding affinity of SP play a dominant initial role in the infectivity of the virus.